Downregulation of high density lipoprotein receptor activity of cultured fibroblasts by platelet-derived growth factor

Abstract

High density lipoprotein (HDL) receptor activity was decreased by the addition of platelet-derived growth factor (PDGF) to cholesterol-loaded cultured human skin fibroblasts. Effects were observed within 12 hours, coinciding with increases in tritiated thymidine incorporation into DNA. The PDGF-mediated decrease in HDL binding was associated with a decrease in cholesterol efflux promoted by HDL3. PDGF exerted reciprocal effects on HDL and low density lipoprotein (LDL) receptor activity. With fibroblasts not loaded with cholesterol, PDGF increased LDL binding without changing HDL receptor activity. With cholesterol-loaded cells, PDGF decreased HDL receptor activity without changing LDL receptor activity. These results show that a reduction in HDL receptor activity is an additional cellular response to PDGF. Decreased HDL-mediated cholesterol efflux may result in retention of cholesterol needed for membrane synthesis in cells stimulated to proliferate.